Suprachoroidal Drug Delivery to the Back of the Eye Using Hollow Microneedles

Abstract

Purpose In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye. Methods A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo. Particle delivery was imaged using brightfield and fluorescence microscopy as well as microcomputed tomography. Results Microneedles were shown to deliver sulforhodamine B as well as nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig, and human eyes. Volumes up to 35 μL were administered consistently. Optimization of the delivery device parameters showed that microneedle length, pressure, and particle size played an important role in determining successful delivery into the suprachoroidal space. Needle lengths of 800–1,000 μm and applied pressures of 250–300 kPa provided most reliable delivery. Conclusions Microneedles were shown for the first time to deliver nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig and human eyes. This shows that microneedles may provide a minimally invasive method for controlled drug delivery to the back of the eye.

Microneedle-Assisted Permeation of Lidocaine Carboxymethylcellulose with Gelatine Co-polymer Hydrogel

“…It is a painless method of micro-injection for not hitting pain receptors 88 concentrated in the dermal layer of skin (19). The planar surface and geometrical properties of 89 the microneedles, and the texture of skin, which is relatively impermeable to large aqueous, 90 active molecules and drug molecules in a bulk polymeric formulation, can increase permeation 91 through the viable epidermal layer of skin via micro channel cavities created by microneedles 92 (20,21 …”

Delivery of therapeutics for deep-seated ocular conditions – status quo

“…[32,33] As discussed above, periocular or topical administration when used for posterior ocular delivery faces many challenges. As such, injections to deliver drug to posterior target ocular tissue have been more commonly used.…”

“…[32] Intravitreal injection can also be formulated to provide a sustained release. [32] However, intravitreal injections still face significant limitations; the first involves a risk of endophthalmitis, the second carries a risk of exposing unintended tissues by the drug and lastly, the administration is very invasive.…”

“…In situ gels are a drug delivery system which when administered in a liquid form phase shift into a gel or solid form once reaching the conjunctival cul-de-sac. [39] Despite typically being administered [1,4] ) 2 Ability to modify the rate of release of drug [1,4] 3 Ability to provide a stimuli-sensitive drug release mechanism [1,4] 1 Allow sustained release of drug [35,36] 2 Prolonged therapeutic duration at site of action [35,36] 3 Can overcome limitation of eye drops where drug wastage is an issue [35,36] 1 No blurred vision or irritation with administration [39,40] 2 Prolonged drug retention at desired tissue in the eye [39,41] 3 Decreased frequency of dosing [40,41] 1 Both hydrophilic or lipophilic drugs can be used [32] 2 Increase drug penetration across conjunctival and corneal epithelium [32] 3 Display ability to provide sustained released [32,46] 4 Decreased frequency of dosing [46] Cons 1 Low reproducibility [4,48] 2 Instability of the macromolecules during production stage [4,48] 3 Variable size distribution [4,48] 4 Expensive [4,48] 1 May increase intraocular pressure and induce local systemic adverse effects [38] 2 Inconvenient administration for patient [38] 3 Risk of tissue damage if administered incorrectly [38] 1 Lack of cell specificity [41] 2 Requires intravitreal administration due to poor penetration & specificity [40] 3 Expensive …”

Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery

“…dry-film of ovalbumin protein antigen was coated over the limited surface area of solid microneedles prior to insertion and subsequent delivery to the interstitial fluid to evoke an immune response 45 ); or hollow microneedles that can connect to a backing layer reservoir or syringe (e.g. miniaturized versions of traditional hypodermic needles 1,3 ), thus increasing the potential volume for drug delivery. 50 Although there has been significant pre-clinical evaluation of microneedle technologies, relatively few platforms have been brought through clinical trials.…”